1. Field of the Invention
There are many situations where one wishes to detect a minor amount of DNA in a small population of cells. This situation is particularly applicable to transformation of cells, where the multiplication of the cells is relatively slow, so that the availability of a sufficient number of cells to provide for a sufficient amount of the nucleic acid to be able to detect in ordinary samples may take days, weeks or months. Illustrative of such situations, where long periods of time may be involved, is the situation with transformation of plant cells where several weeks or months may be involved to obtain a sufficient amount of tissue culture to perform a Southern or Northern hybridization analysis. An additional example would be a case where an assay for transient expression is desired in cells microinjected with DNA or RNA. An immediate assay would allow for monitoring of the fate of injected nucleic acids as well as detection of transcription from injected DNA molecules. Therefore, techniques which allow for hybridizations with a small number of cells can be of great interest and importance in these situations.
2. Description of the Prior Art
Hybridization techniques are described in Thomas, Proc. Natl. Acad. Sci. USA (1980) 77:5201-5205; White and Bancroft, J. Biol. Chem. (1982) 257:8569-8572; and Manzari et al., Proc. Natl. Acad. Sci. USA (1983) 80:11-15. See also Maniatis et al., (1982) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp. 309ff. Techniques describing hanging drops include Edstrom, (1964) In: Methods in Physiology (D. M. Prescott, ed.) New York, Academic Press, pp. 417-447 and Scalenghe et al., Chromasoma (Berl.) (1981) 82:205-216.